Cell death and regenerative proliferation pathways in hepatocellular carcinoma: The effect of furan on B6C3F1 mouse global gene expression in liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Anna Jackson
PROVIDER: E-GEOD-48644 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action. In this study we examined the transcriptional response in liver tissue of female B6C3F1 mice to BrdU treatment (in drinking water for 5 days before sacrifice). This was a toxicogenomic study in which mice were also exposed to 0, 1 or 8 mg/kg bw furan (by oral gavage) for 3 weeks. Mice were sacrificed four hours after the final furan exposure. Each dose group had 4-5 biological replicates. We used a two-colour reference design and SurePrint G3 Mouse GE 8x60K microarrays (Agilent). Please note that data for all non-BrdU treated animals was previously reported in GEO [GSE48644]. All samples (with or without BrdU) were part of the same randomized block design for the microarrays.
2014-07-01 | E-GEOD-54078 | biostudies-arrayexpress
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action. Adult female B6C3F1 mice were exposed to 1, 2, 4 or 8 mg/kg bw furan or vehicle control (corn oil) for three weeks and sacrificed four hours after the final exposure.
2014-01-10 | GSE48644 | GEO
Project description:Benzo(a)pyrene is a well-established human carcinogen in humans and rodents. In the present study, we sought to determine the dose- and time-dependent changes in gene expression upon oral exposure to benzo(a)pyrene. Adult male B6C3F1 mice were exposed to four doses of benzo(a)pyrene or vehicle control for three days and sacrificed 4 or 24 hours after the final exposure. This experiment examined the hepatic transcriptional response of male mice exposed to BaP for 3 days at four different doses, including D1 (300 mg/kg BW/day), D2 (150 mg/kg BW/day), D3 (50 mg/kg BW/day) and D4 (5 mg/kg BW/day), and one control. Each dose group was further examined at 2 time points, 4 hours and 24 hours, following the final exposure. Each dose group and time point had 4-5 biological replicates. There were a total 46 samples (arrays) included in the final analysis using a two-colour reference design.
2015-07-01 | E-GEOD-43633 | biostudies-arrayexpress
Project description:Benzo(a)pyrene is a well-established human carcinogen in humans and rodents. In the present study, we sought to determine the dose- and time-dependent changes in gene expression upon oral exposure to benzo(a)pyrene. Adult male MutaTMMouse were exposed to three doses of benzo(a)pyrene or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure. This experiment examined the forestomach transcriptional response of male mice exposed to BaP for 28 days at three different doses, including D1 (25 mg/kg BW/day), D2 (50 mg/kg BW/day), and D3 (75 mg/kg BW/day) and vehicle control. Each dose group was examined 72 hours following the final exposure. Each dose group and time point had 4-5 biological replicates. There were a total 17 samples (arrays) included in the final analysis using a two-colour reference design.
2013-09-27 | E-GEOD-43438 | biostudies-arrayexpress
Project description:Furan is a widely used industrial chemical and a common contaminant in heated foods. Chronic furan exposure has been shown to cause cholangiocarcinoma and hepatocellular tumors at doses of 2 mg/kg bw/day with gender differences in frequency and severity. The hepatic transcriptional alterations induced by low doses of furan (doses below those inducing liver tumors) and the potential mechanisms underlying gender differences are largely unexplored. We used DNA microarrays to examine the global hepatic mRNA and microRNA transcriptional profiles of male and female rats exposed to 0, 0.03, 0.12, 0.5 or 2 mg/kg bw/day furan over 90 days. Marked gender differences in gene expression responses to furan were observed, with many more altered genes in exposed males than females, confirming the increased sensitivity of males even at the low doses. Pathway analysis supported that key events in furan-induced hepatotoxicity in males included gene expression changes related to oxidative stress, apoptosis and inflammatory response, while pathway changes in females were consistent with primarily adaptive responses (regeneration). Pathway benchmark doses (BMDs) were estimated and compared to relevant apical endpoints. Transcriptional BMDs could be examined in males, they ranged from 0.08 M-bM-^@M-^S 1.43 mg/kg bw/day and approximated those derived from traditional histopathology. MiR-34a (a target of P53 signalling) was the only microRNA significantly increased at the 2 mg/kg bw/day, providing evidence in support of the importance of apoptosis and cell proliferation in furan hepatotoxicity. Overall, this study demonstrates the use of transcriptional profiling to discern mode of action and mechanisms involved in gender differences. A total of 50 RNA samples (5 female and 5 male rats per dose group, 5 dose groups total) were labelled with Cyanine 5-CTP using Low Input Quick Amp Labelling kits (Agilent Technologies Inc.) following the manufacturerM-bM-^@M-^Ys instruction. Universal rat reference total RNA (Agilent Technologies Inc.) was labelled with Cyanine 3-CTP. Cy5-sample cRNA and Cy3-reference cRNA were hybridized to Agilent G4853A SurePrint G3 Rat GE 8 X 60K microarrays (Agilent Technologies Inc.). One microarray from the male group did not pass the quality control and was eliminated from further analyses
2014-10-30 | E-GEOD-62806 | biostudies-arrayexpress
Project description:Furan is a widely used industrial chemical and a common contaminant in heated foods. Chronic furan exposure has been shown to cause cholangiocarcinoma and hepatocellular tumors at doses of 2 mg/kg bw/day with gender differences in frequency and severity. The hepatic transcriptional alterations induced by low doses of furan (doses below those inducing liver tumors) and the potential mechanisms underlying gender differences are largely unexplored. We used DNA microarrays to examine the global hepatic mRNA and microRNA transcriptional profiles of male and female rats exposed to 0, 0.03, 0.12, 0.5 or 2 mg/kg bw/day furan over 90 days. Marked gender differences in gene expression responses to furan were observed, with many more altered genes in exposed males than females, confirming the increased sensitivity of males even at the low doses. Pathway analysis supported that key events in furan-induced hepatotoxicity in males included gene expression changes related to oxidative stress, apoptosis and inflammatory response, while pathway changes in females were consistent with primarily adaptive responses (regeneration). Pathway benchmark doses (BMDs) were estimated and compared to relevant apical endpoints. Transcriptional BMDs could be examined in males, they ranged from 0.08 – 1.43 mg/kg bw/day and approximated those derived from traditional histopathology. MiR-34a (a target of P53 signalling) was the only microRNA significantly increased at the 2 mg/kg bw/day, providing evidence in support of the importance of apoptosis and cell proliferation in furan hepatotoxicity. Overall, this study demonstrates the use of transcriptional profiling to discern mode of action and mechanisms involved in gender differences. Total RNAs from 16 liver samples (4 males and 4 females from control and 2 mg/kg bw/day dose groups) were processed using the miRNA Complete Labelling and Hybridization kit (Agilent Technologies Inc.). Labelled RNA was hybridized on 8 X 15K Agilent rat miRNA microarray slides. Arrays were scanned using an Agilent G2505B scanner (5 ?M resolution). Feature extraction (version 10.7.3.1, Agilent Tech. Inc.) was used to acquire the fluorescence intensity of each probe.
2014-10-30 | E-GEOD-62807 | biostudies-arrayexpress
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action.
2014-07-01 | GSE54078 | GEO
Project description:In this study, we evaluated the utility of microRNA (miRNA) profiling in female B6C3F1 mouse liver to indicate mechanisms of liver perturbation due to short-term exposure of the known rodent liver hepatotoxicant and carcinogen, furan. Analyses indicated a robust dose response for 34 miRNAs to furan and involvement of p53-linked pathways in furan-mediated hepatotoxicity. Overall, these results indicate mechanistic involvement of miRNA in furan carcinogenicity and provide evidence of their potential utility as accessible biomarkers of exposure and disease.
2023-09-05 | GSE224206 | GEO
Project description:Polycyclic aromatic hydrocarbons (PAHs) are widely distributed, carcinogenic environmental contaminants produced as a consequence of the incomplete combustion of fossil fuels. Benzo[a]pyrene (BaP) is a very extensively studied prototypical PAH. We recently reported a complete lack of change in microRNA (miRNA) expression in adult mouse liver following oral gavage with BaP despite a robust transcriptome response. We hypothesized that hepatic miRNAs may not be highly responsive to the treatment. Here, we analyse the pulmonary mRNA and miRNA response to BaP in the same mice. Adult male B6C3F1 mice were exposed to 5, 50, 150 and 300 mg/kg BaP by oral gavage for three consecutive days and sacrificed 4 or 24 hours after the last exposure. Serum clinical chemistry and DNA adduct levels in whole lung and liver tissues were analysed at both the time points for all the doses. Acute exposure to BaP resulted in modest decreases in serum inorganic phosphorous, calcium, glucose, alkaline phosphatase and lactate dehydrogenase in animals treated with 300 mg/kg BaP. 32P postlabeling of DNA revealed similar increases in BaP-DNA adducts in both lungs and livers of exposed mice in a dose dependent manner at the 4 hour time point. Using DNA microarrays, pulmonary mRNA and miRNA expression was analysed 4 hours after the final exposure. Over 1,000 genes were statistically differentially expressed (fold change > 1.5 and p < 0.05), encompassing numerous pathways including: oxidative stress, xenobiotic metabolism, cell proliferation, cell cycle, B and T-cell receptor signalling and primary immunodeficiency signalling pathways. Analysis of miRNA profiles revealed downregulation of miR-150, miR-142-5p, 142-3p and upregulation of miR-34c and miR-29b. These miRNAs are involved in various biological processes including immune response, cell proliferation and cell cycle, which are also the main pathways affected at the gene expression level. As BaP exposure does not result in hepatocarcinogenicity, but does cause lung cancer, these miRNAs may play an important role in the outcome of the exposure and be more predictive of carcinogenesis. Keywords: mRNA, miRNA, Pulmonary, non-target tissue, Toxicogenomics, Benzoapyrene Adult male B6C3F1 mice were exposed to 5, 50, 150 and 300 mg/kg BaP by oral gavage for three consecutive days and sacrificed 4 or 24 hours after the last exposure. Serum clinical chemistry and DNA adduct levels in whole lung and liver tissues were analysed at both the time points for all the doses. Using DNA microarrays, pulmonary mRNA and miRNA expression was analysed 4 hours after the final exposure. This submission only contains the 4hr time point, at control, 150mg/kg and 300mg/kg (except for the liver study where only the control and 300mg/kg samples were used).
2011-10-03 | E-GEOD-24751 | biostudies-arrayexpress
Project description:Furan is a widely used industrial chemical and a common contaminant in heated foods. Chronic furan exposure has been shown to cause cholangiocarcinoma and hepatocellular tumors at doses of 2 mg/kg bw/day with gender differences in frequency and severity. The hepatic transcriptional alterations induced by low doses of furan (doses below those inducing liver tumors) and the potential mechanisms underlying gender differences are largely unexplored. We used DNA microarrays to examine the global hepatic mRNA and microRNA transcriptional profiles of male and female rats exposed to 0, 0.03, 0.12, 0.5 or 2 mg/kg bw/day furan over 90 days. Marked gender differences in gene expression responses to furan were observed, with many more altered genes in exposed males than females, confirming the increased sensitivity of males even at the low doses. Pathway analysis supported that key events in furan-induced hepatotoxicity in males included gene expression changes related to oxidative stress, apoptosis and inflammatory response, while pathway changes in females were consistent with primarily adaptive responses (regeneration). Pathway benchmark doses (BMDs) were estimated and compared to relevant apical endpoints. Transcriptional BMDs could be examined in males, they ranged from 0.08 – 1.43 mg/kg bw/day and approximated those derived from traditional histopathology. MiR-34a (a target of P53 signalling) was the only microRNA significantly increased at the 2 mg/kg bw/day, providing evidence in support of the importance of apoptosis and cell proliferation in furan hepatotoxicity. Overall, this study demonstrates the use of transcriptional profiling to discern mode of action and mechanisms involved in gender differences.
2014-10-30 | GSE62807 | GEO